Abstract
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J Biol Chem. 2026 Feb 5;302(4):111244. doi: 10.1016/j.jbc.2026.111244. Online ahead of print.
Allosteric properties of mammalian ALOX15 orthologs.
Yang J(1), Borchert A(1), Kuhn H(2).
Author information: (1)Department of Biochemistry, Charité - University Medicine Berlin, Corporate Member of Freie Universität Berlin and Humboldt Universität zu Berlin, Berlin, Germany. (2)Department of Biochemistry, Charité - University Medicine Berlin, Corporate Member of Freie Universität Berlin and Humboldt Universität zu Berlin, Berlin, Germany. Electronic address: hartmut.kuehn@charite.de.
Lipoxygenases (arachidonic acid lipoxygenase [ALOX]) are non-heme iron-containing dioxygenases that catalyze the oxygenation of polyenoic fatty acid-containing lipids to their corresponding hydroperoxy derivatives. These enzymes are widely distributed in highly developed plants and animals. In bacteria, they rarely occur, but they have not been detected in archaea and viruses. The human genome involves six functional ALOX genes (ALOX15, ALOX15B, ALOX12, ALOX12B, ALOXE3, and ALOX5) encoding for six different isoenzymes. The mouse genome carries an orthologous gene for each human ALOX gene, but in addition, an Aloxe12 gene has been identified in this species. The application of isoenzyme-specific loss-of-function strategies suggested that the coding multiplicity may not be interpreted as a sign of functional redundancy. In fact, the different isoenzymes apparently fulfill different biological functions. Mammalian ALOX15 orthologs are allosteric enzymes, but the molecular basis for their allosteric properties remains controversial. In fact, two alternative hypotheses (the presence of allosteric binding sites at enzyme monomers versus ALOX15 dimers consist of an allosteric and a catalytic monomer) have been introduced, and this review is aimed at critically evaluating the pros and cons of these two mechanistic scenarios.
Copyright © 2026 The Authors. Published by Elsevier Inc. All rights reserved.
DOI: 10.1016/j.jbc.2026.111244 PMCID: PMC12993299 PMID: 41654134
Conflict of interest statement: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article.